Project Summary/Abstract Chronic pain is a debilitating health condition that is currently insufficiently treated by available therapies. Ther is a growing need to develop alternatives to treat chronic pain and specifically diabetic neuropathy as diabetes is increasing worldwide and painful neuropathy occurs in 50% of diabetic patients. Recently, the importance of lipids as signaling mediators and their functional significance in nociception has been elucidated. Epoxy-fatty acid metabolites generated by cytochrome P450s mediate analgesia, and we have synthesized small molecule inhibitors of their metabolizing enzyme, the soluble epoxide hydrolase (sEH), to elevate their levels in vivo. With this proposal, we aim to develop a novel and safe oral inhibitor of sEH for the treatment of peripheral neuropathy in diabetic patients. Preclinical studies with our candidate, EC5026, demonstrate efficacy that exceeds current therapies for diabetic neuropathy. Based on efficacy, good PK/ADME properties and stability, EicOsis has selected EC5026 to enter further development stages. EicOsis will work with Blueprint Development Teams to create a development plan and initiate studies to test the safety of EC5026 in Phase 1 clinical trials.